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. 2016 Oct 17;55(43):13529-13532.
doi: 10.1002/anie.201608138. Epub 2016 Sep 26.

Enantioselective Pd-Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2-a]indolone Substrates: Efficient Syntheses of (-)-Goniomitine, (+)-Aspidospermidine, and (-)-Quebrachamine

Beau P Pritchett  1 , Jun Kikuchi  1 , Yoshitaka Numajiri  1 , Brian M Stoltz  2
Affiliations

Enantioselective Pd-Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2-a]indolone Substrates: Efficient Syntheses of (-)-Goniomitine, (+)-Aspidospermidine, and (-)-Quebrachamine

Beau P Pritchett et al. Angew Chem Int Ed Engl. .

Abstract

The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (-)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (-)-quebrachamine, are reported herein.

Keywords: alkaloids; allylic alkylation; asymmetric catalysis; quaternary centers; total synthesis.

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Figures

Figure 1
Figure 1
Skeletally Diverse Aspidosperma alkaloids.
Scheme 1
Scheme 1
A) Biogenesis of goniomitine from vincadifformine. B) Effects of C3 substitution on indole-iminium cyclization. C) Retrosynthetic analysis of 5.
Scheme 2
Scheme 2
Suzuki cross-coupling of a 3-bromoindole fragment. [a] AtaPhos = di-tert-butyl(4-dimethylamino)phenylphosphine.
Scheme 3
Scheme 3
Cross-coupling reactivity of α-quaternary DHPI 14b.
Scheme 4
Scheme 4
Completion of the synthesis of (−)-goniomitine.
Scheme 5
Scheme 5
Asymmetric formal syntheses of other Aspidosperma alkaloids.
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References

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    1. For a biomimetic semisynthesis of goniomitine (1) from vincadifformine (4), see: Lewin G, Bernadat G, Aubert G, Cresteil T. Tetrahedron. 2013;69:1622–1627.

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